Pseudomonas aeruginosa kills Staphylococcus aureus in a polyphosphate-dependent manner

Abstract

ABSTRACTDue to their frequent coexistence in many polymicrobial infections, including in patients with burn or chronic wounds or cystic fibrosis, recent studies have started to investigate the mechanistic details of the interaction between the opportunistic pathogensPseudomonas aeruginosaandStaphylococcus aureus.P. aeruginosarapidly outcompetesS. aureusunderin vitroco-cultivation conditions, which is mediated by several ofP. aeruginosa’s virulence factors. Here, we report that polyphosphate (polyP), an efficient stress defense system and virulence factor inP. aeruginosa, plays a role for the pathogen’s ability to inhibit and killS. aureusin a contact-independent manner. We show thatP. aeruginosacells characterized by low polyP level are less detrimental toS. aureusgrowth and survival while the gram-positive pathogen is significantly more compromised by the presence ofP. aeruginosacells that produce high level of polyP. We show that the polyP-dependent phenotype could be a direct effect by the biopolymer, as polyP is present in the spent media and causes significant damage to theS. aureuscell envelope. However, more likely is that polyP’s effects are indirect through the regulation of one ofP. aeruginosa’svirulence factors, pyocyanin. We show that pyocyanin production inP. aeruginosaoccurs polyP-dependent and harmsS. aureusthrough membrane damage and the generation of reactive oxygen species, resulting in increased expression of antioxidant enzymes. In summary, our study adds a new component to the list of biomolecules that the gram-negative pathogenP. aeruginosagenerates to compete withS. aureusfor resources.IMPORTANCEHow do interactions between microorganisms shape the course of polymicrobial infections? Previous studies have provided evidence that the two opportunistic pathogensP. aeruginosaandS. aureusgenerate molecules that modulate their interaction with potentially significant impact on disease outcomes. Our study identified the biopolymer polyP as a new effector molecule that impactsP. aeruginosa’s interaction withS. aureus. We show thatP. aeruginosakillsS. aureusin a polyP-dependent manner, which occurs primarily through the polyP-dependent production of theP. aeruginosavirulence factor pyocyanin. Our findings add a new role for polyP to an already extensive list of functions. A more in-depth understanding of how polyP influences interspecies interactions is critical, as targeting polyP synthesis in bacteria such asP. aeruginosamay have a significant impact on other microorganisms and potentially result in dynamic changes in the microbial composition.